Abstract B157: Investigating associations between smoking history and gene expression in cultured cells

Abstract The purpose of this study includes identifying genes associated with cigarette smoke (CS) in two cell types collected from a racially diverse group of donors to support future studies that examine the genetic basis of cancer health disparities. Smoking is associated with an elevated risk for squamous cell carcinoma and leukemias, impacting skin and whole blood, respectively. However, the transcriptomic impact of CS in cell types from non-diseased tissues from Genotype Tissue Expression (GTEx) project donors remains uncharacterized. Genetic responses to smoking may indicate molecular mechanisms that mediate or protect against the harmful effects of smoking. Our lab published a study characterizing associations between CS and DNA methylation in several tissue types, suggesting that the epigenome is altered by CS across tissues, which may also dysregulate expression. Preliminary data for this study show that CS is associated with gene expression changes in whole blood and skin. However, little is known about the genetic response to smoking in immortalized skin fibroblasts or peripheral blood lymphocytes isolated from skin and whole blood, respectively. Therefore, we conducted a differential gene expression analysis to assess the impact of CS history on gene expression using RNA-sequencing (RNA-seq) data from these cell types, harvested from postmortem donors participating in the GTEx project. Based on observed associations between CS and gene expression in tissues harboring these cells, we hypothesize that smoking could also impact gene expression in cultured fibroblasts and lymphocytes. Associations between smoking and gene expression in each cell type might suggest that the epigenetic memory related to the smoking response was preserved during the transformation and/or culturing processes. Our results show no association between CS exposure and gene expression in either cell type. Future directions include stratifying results to examine smoking-associated changes in expression by race/ethnicity to understand the transcriptomic basis of smoking-induced disparities in skin and whole-blood related cancers. Citation Format: Siyeon Joo, Letonia Copeland-Hardin, Lin Tong, Kathryn Demanelis, Brandon Pierce. Investigating associations between smoking history and gene expression in cultured cells [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr B157.